Le infezioni di cute e tessuti molli

Le infezioni di cute e tessuti molli SCELTE e STRATEGIE TERAPEUTICHE Pierluigi Viale Clinica di Malattie Infettive Policlinico S. Orsola Malpighi

Treatment of complicated skin and skin structure infections in areas with low incidence of antibiotic resistance-a retrospective population based study from Finland and Sweden Jääskeläinen IH, et al. Clin Microbiol Infect 2016;22:383 460 patients; mean age 60.8 years; (60.9% male) 13.3% of patients had bacteraemia, 15.9% were admitted to an Intensive Care Unit 51% underwent at least one surgical intervention. Treatment failure occurred in 28.2%, Initial antibiotic treatment modification to another intravenous drug in 38.5% Gram-positive bacteria were predominantly isolated, Median overall LOS and antimicrobial treatment were 13 and 17 days On average 3.5 (SD 2.1) different antibiotics were used per patient. Oral antimicrobial treatment was continued in 64.3% of patients after discharge. The overall mortality rates in 30 d and in 12 m were 4.1% and 11.8%, respectively 16.4% of patients had a recurrence of SSSI within 12 months.

Treatment of complicated skin and skin structure infections in areas with low incidence of antibiotic resistance-a retrospective population based study from Finland and Sweden Jääskeläinen IH, et al. Clin Microbiol Infect 2016;22:383 Comorbidities 3

% of patients with hospitalisation for SSTI % of patients with complications Skin and Soft Tissue Infections and Associated Complications among Commercially Insured Patients Aged 0 64 Years with and without Diabetes in the U.S. Suaya JA et al, PLoS One 2013 Apr 10;8(4):e60057 2,227,401 SSTI episodes Diabetic patients with SSTIs* are more frequently hospitalised Diabetic patients with SSTIs more likely to be associated with complications P<0.01 P<0.01 Complications: lymphadenitis, necrotising fasciitis, gangrene, osteomyelitis, bacteraemia, septicaemia, sepsis, endocarditis

KEY POINTS for a discussion about TREATMENT STRATEGIES A large number recommendations have been published for the management of skin and soft tissue infections. A significant number of comparative trials has been published but they are referred to a different classifications than guidelines The empirical antibiotic therapy should take into account the patient s initial severity, the extent of infection, and the risk factors for resistant microorganisms. The prescriber should differentiate necrotizing and non-necrotizing infections, although this distinction could be difficult to apply. Optimal therapy is based on a timely and aggressive source control for severe cases

S. aureus - the most prevalent pathogen isolated from csssis and ABSSIs Dryden MS. J Antimicrob Chemother 2010;65(Suppl 3):iii35 iii44. 6

Annual visits to US Emergency Departments for selected acute bacterial skin and skin structure infections

MRSA-ABSSSI is associated with increased risk of mortality and healthcare costs For surgical site infections caused by MRSA vs MSSA : Patients had a 3.4 OR (95% CI: 1.5 7.2) for 90-day mortality Patients had 5.5 days (95% CI: 1.97 9.11) longer hospital stay Additional healthcare costs of $24,113 (95% CI: 4,521 43,704) Engemann JJ, et al. Clin Infect Dis 2003;36(5):592 8. Anderson DJ, et al. PLoS One 2009;4(12):e8305. 8

Risk factors for MRSA-ABSSSI Multivariate ORs and 95% CIs for risk markers for MRSA SSTIs Variable Adjusted OR (95% CI) Previous MRSA infection and colonisation 6.4 (2.1 19.8) Abscess 5.6 (1.8 17.1) Intravenous drug use 4.6 (1.4 16.1) Diabetes mellitus 4.1 (1.4 12.1) Antibiotic use in prior 8 weeks 2.6 (1.2 8.1) Hospital admission or surgery in previous year 2.6 (1.1 11.2) Stenstrom R, et al. Can J Emerg Med 2009;11(5):430 8. 9

Antibiotic treatment patterns across Europe in patients with complicated skin and soft-tissue infections due to MRSA: a plea for implementation of early switch and early discharge criteria. Eckmann C et al, Int J Antimicrob Agents 2014;44:56-64.

Staphylococcus aureus: Resistance Issues Methicillin Resistance Vanco MIC-creep Heterogeneous vancomycin-intermediate strains Daptomycin reduced sensitivity Rifampicin Resistance The secret world of the biofilm NEED FOR NEWS?

NEWS CEFTAROLINE CEFTOBIPROLE DALBAVANCIN TEDIZOLID ORITAVANCIN TELAVANCIN FOSFOMYCIN DELAFLOXACIN OMADACYCLINE

Setting ABSSI with sepsis signs - 1378 pts Drugs CEFTAROLINE FOSAMIL (600 mg every 12 h) or VANCOMYCIN (15 mg/kg every 12 h) plus AZTREONAM (1 g every 8 h) for 5 14 days.

Setting ABSSI with sepsis signs - 761 pts Drugs CEFTAROLINE FOSAMIL (600 mg every 8 h) or VANCOMYCIN (15 mg/kg every 12 h) plus AZTREONAM (1 g every 8 h) for 5 14 days.

Setting ABSSI -1303 pts Drugs DALBAVANCIN at a dose of 1 g given intravenously over a period of 30 minutes on day 1, followed by 500 mg given intravenously over a period of 30 minutes on day 8, or VANCOMYCIN at a dose of 1 g (or 15 mg per kilogram of body weight) given intravenously over a period of 120 minutes every 12 hours for at least 3 days, with an option to switch to oral Linezolid, at a dose of 600 mg every 12 hours, to complete 10 to 14 days of therapy.

Setting ABSSI 698 pts Drugs DALBAVANCIN 1500 mg either as a single intravenous infusion or DALBAVANCIN 1000 mg IV on day 1 followed 1 week later by 500 mg IV.

Safety of Dalbavancin in the Treatment of SSTIs: A Pooled Analysis of Randomized, Comparative Studies. Dunne MW et al, Drug Saf 2016; 39:147 157 Data on adverse events and laboratory assessments collected from 3002 patients enrolled in seven late stage, randomized clinical trials were analyzed for patients receiving dalbavancin or a comparator antibiotic. Overall adverse event rates were similar or lower for patients receiving dalbavancin (799/1778; 44.9 %) compared with those receiving comparator agents (573/1224; 46.8 %, p = 0.012). The most common treatment emergent adverse events were nausea, headache, diarrhea, constipation, vomiting, rash, urinary tract infection, pruritus,and insomnia

Antibiotics currently or soon to be clinically available for infection caused by MRSA Class Agent Dose Comments Glycopeptides Vancomycin 1-1.5gm bd 15mg/kg Concern over MIC creep and resistance. Teicoplanin 400mg bd,od 6-10 mg/kg Oritavancin 1200mg sd Single dosing Similar issues as with vancomycin Dalbavancin 1500 mg sd Once weekly/ single dosing Oxazolidanones Linezolid 600mg bd Concerns about toxicity and nephropathy. Useful for IV/PO switch Tedizolid 200mg od Possibly fewer adverse events than linezolid Glycylcycline Tigecycline 100mg, then 50mgbd Concerns about safety Lipopeptide Daptomycin 4-6mg/kg Check CK (and INR if required) before treatment Beta-lactams Ceftaroline 600mg tid 1 st beta-lactam with anti-mrsa activity, Possible more rapid early clinical response. Dryden MS. Curr Opinion Infect Dis 2014; 27 116-124

EMPIRICAL 1 ST LINE MANAGEMENT of HOSPITALIZED CA-cSSTI PAIN RELATED TO CLINICAL FINDINGS DEMARCATE, SLOWLY EVOLVING PAIN UNRELATED TO CLINICAL FINDINGS NOT DEMARCATE, RAPIDLY EVOLVING NON NECROTIZING NECROTIZING? SEPSIS > SEVERE SEPSIS LRINEC SCORE > 8 AMOXI-CLAV 2.2 g/6 h +/- CLINDAMYCIN 600 mg/6 h

EMPIRICAL 1 ST LINE MANAGEMENT of HA- SSTI (SWI) SUPERFICIAL INCISIONAL SSI DEEP INCISIONAL SSI STERNAL WOUND INFECTION DOXYCYCLINE 100 mg/12 h + RIFAMPICIN 600 mg/24 h MICROBIOLOGY MRSA 40% MRSE >70% VANCOMICIN by CI + RIFAMPICIN 600 mg/24 h DALBAVANCIN? LINEZOLID 600 mg/12 h TEDIZOLID?

EMPIRICAL 1 ST LINE MANAGEMENT of HOSPITALIZED CA-cSSTI PAIN RELATED TO CLINICAL FINDINGS DEMARCATE, SLOWLY EVOLVING PAIN UNRELATED TO CLINICAL FINDINGS NOT DEMARCATE, RAPIDLY EVOLVING NON NECROTIZING NECROTIZING? SEPSIS AMOXI-CLAV 2.2 g/6 h +/- CLINDAMYCIN 600 mg/6 h > SEVERE SEPSIS LRINEC SCORE > 8 CEFTAROLINE TID / CEFTOBIPROLE for selected pts? DAPTOMYCIN for selected pts? DALBAVANCIN for home treatment/early discharge strategies? DALBAVANCIN for recurrences management?